This invention is directed to a vascular prosthesis having a well-defined pore structure to allow uninterrupted ingrowth of connective tissue into the wall of the prosthesis. Furthermore, mechanical properties of the prosthesis are matched with mechanical properties of a host vessel, thereby overcoming problems of compliance mismatch.
Since the early 1950""s, when Voorhees observed an essentially thrombus-free silk thread in a prosthesis explanted from a dog, various polymeric materials have been evaluated for use in porous vascular prostheses. Most commercially available synthetic vascular grafts presently in use are made from either expanded polytetrafluoroethylene (e-PTFE), or woven, knitted, or velour design polyethylene terephthalate (PET or Dacron). Dacron grafts are normally used for large vessel replacement (12-22 mm), whereas e-PTFE is generally used for intermediate diameters (6-12 mm). These conventional prosthetic vascular grafts do not permit unrestricted vessel ingrowth from surrounding tissue due mostly to ingrowth spaces that are either too narrow or discontinuous. When used for smaller diameters, these grafts often fail early due to occlusion by thrombosis (fibrous tissue build up) or kinking, or at a later stage because of anastomotic or neointimal hyperplasia (exuberant muscle growth at the interface between artery and graft). Compliance mismatch between the host artery and the synthetic vascular prosthesis, which may result in anastomotic rupture, disturbed flow patterns and increased stresses, is thought to be a causative factor in graft failure. Other causative factors may include the thrombogenicity of the grafts or the hydraulic roughness of the surface, especially in crimped grafts.
In attempts to facilitate ingrowth, the pore size of commercial e-PTFE grafts has been increased. Due to the irregular structure of the pores (between the nodes and internodular fibers), the available ingrowth spaces rapidly narrow down to sub-arteriole dimensions. Various researchers have produced xe2x80x9cfoam typexe2x80x9d grafts, and although compliance matching was achieved to some extent by some, the structures obtained by them have certain disadvantages that prohibit or inhibit the ingrowth of connective tissue. These disadvantages include closed external and/or internal surfaces, closed or semi-closed cell structures with little or no inter-pore communication, and irregularly shaped and sized pores due to irregular filler materials used in the processes.
Because of their unique combination of physical, chemical and biocompatible properties, polyurethanes have been studied and used in medical devices for over thirty years. Enzymatic hydrolysis, auto-oxidation, mineralization, and biologically induced environmental stress cracking of polyester- and polyetherurethanes have led manufacturers of medical polyurethanes to develop more specialized formulations to prevent these occurrences. These new generation polyurethane elastomers are being increasingly accepted as the biomaterials of choice in most applications, especially those requiring compliance. It is not surprising, therefor, that many researchers have used various polyurethane compositions (and other elastomers) to produce vascular grafts. Salt casting, phase inversion, spraying, and replamineform techniques have been used to produce sponge-like structures containing ill-defined pores, while filament winding and electrostatic spinning result in the formation of filamentous or fibrous structures. In the production of many of these devices, researchers have been able to approximate the compliance of natural blood vessels by careful manipulation of the process variables. Nevertheless, the performance of these experimental grafts is generally unsatisfactory. This indicates that compliance matching alone does not result in the desired healing patterns.
There is thus a need or desire in the vascular prosthesis industry for a vascular graft having a well-defined pore structure in its walls to allow uninterrupted ingrowth of connective tissue into the walls of the prosthesis, wherein the problems of compliance mismatch are overcome.
The present invention is directed to a graft with a porous wall structure containing interconnecting, uniformly shaped pores (i.e. voids) having average diameters between 10 and 300 xcexcm, more preferably 40-110 xcexcm. The standard deviation of the diameters of the pores is typically less than 20 xcexcm, more preferably less than 10 xcexcm. The openings between the pores are typically in the order of 1100 xcexcm, more typically 20-50 xcexcm, depending on the size of the pores. The pores (i.e. voids) in the structure have well-defined, preferably spherical shapes, and the sizes of the ingrowth spaces are readily optimized for uninterrupted tissue and vessel ingrowth. The problem of compliance mismatch encountered with conventional grafts is also addressed by matching mechanical properties of the graft with mechanical properties of a host vessel. These mechanical properties include smoothness, elasticity and structural integrity.
Several different methods can be used to produce the graft of the present invention. In one method, a tube is fashioned from an elastomeric polymer, for example, by molding an admixture of polymer, solvent (for the polymer), and spherical, soluble microbeads of a desired diameter. Extraction of the beads and precipitation of the polymer renders a tubular structure containing well-defined pores (in the tube wall) suitable for use as a synthetic, small-diameter vascular graft prosthesis.
In other methods, a paste comprising a polymer solution, for example, and an extractable filler is prepared and either rolled onto a mandrel, deposited as layers onto a mandrel, or extruded through an annular orifice. The polymer is then precipitated and the filler is extracted.
An alternative method for making the invention involves melt extrusion of a thermoplastic elastomer with blowing agents to create porosity.
With the foregoing in mind, it is a feature and advantage of the invention to provide a synthetic vascular graft that contains interconnecting, well-defined pores.
It is also a feature and advantage of the invention to provide a graft with a porous wall structure containing pores in a very narrow size range.
It is another feature and advantage of the invention to provide a graft with well-defined pores wherein the sizes of the ingrowth spaces are readily optimized for uninterrupted tissue and vessel ingrowth into the wall of the prosthesis.
It is yet another feature and advantage of the invention to provide a graft wherein mechanical properties of the graft are matched with mechanical properties of the host vessel, thereby overcoming problems of compliance mismatch.
It is a further feature and advantage of the invention to provide a method for producing a graft with interconnecting, well-defined pores.